The genes in the mouse H-2 major histocompatibility complex (MHC) determine a diversity of functions associated with immune recognition and reaction. Three of these genes, H-2K, H-2D and H-2L encode antigens involved in allograft rejection and T-lymphocyte responses. The purpose of this work is to determine the primary structure of these molecules in order to better understand their function and mechanism of action. The determination of the amino acid sequence of the extracellular portion (approximately 280 residues) of the H-2Kb MHC antigen has been completed and that of the transmembrane portion (approximately 25 residues) and the intracellular portion (approximately 35 residues) of this molecule are nearing completion. For comparative purposes, major portions of the primary structure of four other H-2 molecules (H-2Db, Kd, Ld and Dd) have been completed and recent immunoprecipitation studies suggest the presence of a third H-2 molecule encoded at the D-end of the MHC which has tentatively been designated H-20. The determination of the amino acid sequence of murine beta 2m, the light chain associated with certain molecules encoded by the MHC has resulted in the detection of at least one variable position. Previous studies of this molecule isolated from humans and rabbits have indicated it to be nonpolymorphic.